The synthesis of aza-dipyrromethenes as potential pdt agents and measurement of singlet oxygen generation.

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Abstract

Photodynamic therapy is a relatively new treatment for various cancers and other diseases using a photosensistiser that produces cytotoxic singlet oxygen (1O2) after light irradiation. Current approved photosensitisers have limitations, such as a low extinction coefficient in the desired therapeutic wavelength of absorption (600 – 900 nm), as in the case of Photofrin®. The discovery of improved photosensitisers is essential if photodynamic therapy is to become more common and successful than other treatments. In this research a selection of aza-dipyrromethenes and their intermediates were synthesised to create photosensitisers that were able to absorb light within the therapeutic wavelength and create 1O2 by energy transfer from the photosensitiser. As shown by others, receptors can be used to control 1O2 generation via photoinduced electron transfer (PET). The synthesis of aza-dipyrromethenes using intermediates containing pyridine groups and crown ethers was unsuccessfully attempted to create photosensitisers with receptors sensitive to environmental factors, such as pH and sodium ion concentration, in the hope that such receptors would control 1O2 generation via PET. Evaluation of the synthesised compounds for use as photosensitisers was carried out using a range of light sources. Measurement of singlet oxygen generated was carried out using diphenylbenzofuran (DPBF), a singlet oxygen scavenger, and the depletion of the absorbance of DPBF used to quantify the rate of 1O2 generation. Comparison with methylene blue, a known photosensitiser, gave a singlet oxygen quantum yield of the compounds to evaluate their efficacy as potential photosensitisers. It has been shown from the photophysical data that the synthesised compounds in this research absorb within the desired range, (600 – 900 nm), but 1O2 generation is insufficient and further modification of the aza-dipyrromethene scaffold is needed to create useful photosensitisers for photodynamic therapy.